A Study of the Safety and Effectiveness of Lyophilized Certolizumab Pegol in the Treatment of Signs and Symptoms of Rheumatoid Arthritis and in Prevention of Joint Damage in Patients With Active Rheumatoid Arthritis

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00175877
• Collaborator: (none)
• Enrollment: 857
• Locations: 121
• Arm: 1
• Duration (Months): 80
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

An open ended study in which patients who completed the double-blind study CDP870-027 [NCT00152386] are given Certolizumab Pegol (CZP) and assessed for signs and symptoms of Rheumatoid Arthritis (RA).

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: Certolizumab Pegol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 857 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Multi-centre, Open-label, follow-on Study to CDP870-027, to Assess the Efficacy and Safety of Lyophilized CDP870 an Engineered Human Anti-TNF PEG Conjugate, as Additional Medication to Methotrexate, in the Treatment of Signs and Symptoms and Preventing Structural Damage in Patients With Active Rheumatoid Arthritis
• Study Start Date: Jun 1, 2005
• Actual Primary Completion Date: Feb 1, 2012
• Actual Study Completion Date: Feb 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Certolizumab Pegol All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection.	Biological: Certolizumab Pegol; Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.; Other Names: Cimzia

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With at Least One Adverse Event (AE) From First Certolizumab Pegol (CZP) Dose up to Approximately 7 Years [From first dose of CZP to the end of the open-label study (approximately 7 years)]

   An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. First dose of Certolizumab Pegol (CZP) was at Baseline of the preceding double-blind study [NCT00152386] for subjects randomized to CZP, or at Entry Visit (Week 0) of this study for subjects randomized to Placebo.

2. Percentage of Subjects With at Least One Serious Adverse Event (SAE) From First Certolizumab Pegol (CZP) Dose up to Approximately 7 Years [From first dose of CZP to the end of the open-label study (approximately 7 years)]

   A SAE is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalisation or prolongation of existing hospitalisation Results in persistent or significant disability/incapacity, or Is a congenital anomaly or birth defect Is as infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above First dose of CZP was at Baseline of the preceding double-blind study [NCT00152386] for subjects randomized to CZP, or at Entry Visit (Week 0) of this study for subjects randomized to Placebo.

3. Percentage of Subjects Who Withdrew Due to an Adverse Event (AE) During the Study [From Entry Visit (Week 0) to the end of the study (approximately 6.5 years)]

   An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. The results of this Primary Outcome Measure are summarized from the Adverse Event pages of the Case Report Forms.

Secondary Outcome Measures

1. Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 48 [From Baseline of the preceding double-blind study to Week 48 of the open-label study]

   The assessments are based on a 20 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

2. Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 96 [From Baseline of the preceding double-blind study to Week 96 of the open-label study]

   The assessments are based on a 20 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

3. Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 144 [From Baseline of the preceding double-blind study to Week 144 of the open-label study]

   The assessments are based on a 20 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

4. Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 192 [From Baseline of the preceding double-blind study to Week 192 of the open-label study]

   The assessments are based on a 20 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

5. Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 240 [From Baseline of the preceding double-blind study to Week 240 of the open-label study]

   The assessments are based on a 20 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

6. Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Completion/Withdrawal [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

   The assessments are based on a 20 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

7. Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 48 [From Baseline of the preceding double-blind study to Week 48 of the open-label study]

   The assessments are based on a 50 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

8. Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 96 [From Baseline of the preceding double-blind study to Week 96 of the open-label study]

   The assessments are based on a 50 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

9. Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 144 [From Baseline of the preceding double-blind study to Week 144 of the open-label study]

   The assessments are based on a 50 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

10. Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 192 [From Baseline of the preceding double-blind study to Week 192 of the open-label study]

    The assessments are based on a 50 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

11. Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 240 [From Baseline of the preceding double-blind study to Week 240 of the open-label study]

    The assessments are based on a 50 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

12. Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Completion/Withdrawal [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

    The assessments are based on a 50 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

13. Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 48 [From Baseline of the preceding double-blind study to Week 48 of the open-label study]

    The assessments are based on a 70 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

14. Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 96 [From Baseline of the preceding double-blind study to Week 96 of the open-label study]

    The assessments are based on a 70 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

15. Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 144 [From Baseline of the preceding double-blind study to Week 144 of the open-label study]

    The assessments are based on a 70 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

16. Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 192 [From Baseline of the preceding double-blind study to Week 192 of the open-label study]

    The assessments are based on a 70 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

17. Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 240 [From Baseline of the preceding double-blind study to Week 240 of the open-label study]

    The assessments are based on a 70 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

18. Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Completion/Withdrawal [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

    The assessments are based on a 70 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.

19. Change From Baseline of the Preceding Double-Blind Study to Week 96 in Modified Total Sharp Score (mTSS) [From Baseline of the preceding double-blind study to Week 96 of the open-label study]

    The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively, as assessed by x-rays of the hands and feet. The score ranges from 0 to 448 with higher scores representing greater damage. A negative value in mTSS change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

20. Change From Baseline of the Preceding Double-Blind Study to Completion/Withdrawal Visit in Health Assessment Questionnaire - Disability Index (HAQ-DI) Total Score [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

    The HAQ-DI assesses the degree of difficulty experienced in eight domains (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Gripping, Other Activities) of daily living activities using 20 questions. The HAQ-DI is calculated by summing the domain scores and dividing them by the number of domains. It ranges from 0 (no difficulty) to 3 (unable to do). Negative values indicate an improvement from Baseline to the Post-Baseline Visit with larger negative values showing a better improvement.

21. Change From Baseline to Completion/Withdrawal Visit in Duration of Morning Stiffness [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

    Morning stiffness is defined as the time in hours elapsed between the time of usual awakening (even if not in the morning) and the time the subject is as limber as he/she will be during a day involving typical activities. A negative value in duration of morning stiffness change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

22. Change From Baseline to Completion/Withdrawal Visit in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28[ESR]) [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

    DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline.

23. Percentage of Subjects With Good European League Against Rheumatism (EULAR) Response at Completion/Withdrawal Visit [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

    Good EULAR response is defined as Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28[ESR]) improvement from Baseline of the preceding double-blind study > 1.2 and DAS28[ESR] value < 3.2.

24. Change From Baseline to Completion/Withdrawal Visit in Short-Form Health Survey (SF-36) Item Questionnaire Physical Component Summary (PCS) Score [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

    The SF-36 is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept PCS score are scored to yield values between 0 (worst) and 100 (best).

25. Change From Baseline to Completion/Withdrawal Visit in Short-Form Health Survey (SF-36) Item Questionnaire Mental Component Summary (MCS) Score [From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)]

    The SF-36 is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept MCS score are scored to yield values between 0 (worst) and 100 (best).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Patients must have either failed to achieve American College of Rheumatology 20 % Response Criteria (ACR20) at Weeks 12 and 14 in C87027 [NCT00152386], or must have completed the entire Week 52 assessment of C87027 [NCT00152386] trial.

Exclusion Criteria:

• A diagnosis of any other inflammatory Arthritis (e.g. Psoriatic Arthritis or Ankylosing Spondylitis)

• A secondary, non-inflammatory type of Arthritis (e.g. Osteoarthritis or Fibromyalgia) that in the Investigator's opinion is symptomatic enough to interfere with evaluation of the effect of CDP870 on the patient's primary diagnosis of Rheumatoid Arthritis

• Any concomitant biological therapy

• Any experimental therapy, within or outside a clinical trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	152	Huntsville	Alabama	United States
2	148	San Diego	California	United States
3	153	Danbury	Connecticut	United States
4	133	Ocala	Florida	United States
5	140	Orlando	Florida	United States
6	150	Orlando	Florida	United States
7	145	Sarasota	Florida	United States
8	136	Tampa	Florida	United States
9	157	Coeur d'Alene	Idaho	United States
10	155	Springfield	Illinois	United States
11	134	Wheaton	Maryland	United States
12	151	Saint Louis	Missouri	United States
13	156	Lincoln	Nebraska	United States
14	135	Charlotte	North Carolina	United States
15	147	Cleveland	Ohio	United States
16	158	Dayton	Ohio	United States
17	139	Charleston	South Carolina	United States
18	137	Austin	Texas	United States
19	143	San Antonio	Texas	United States
20	12	Buenos Aires		Argentina
21	14	Capital Federal		Argentina
22	1	Capital Federal		Argentina
23	9	Capital Federal		Argentina
24	8	Ciudad Autonoma de Buenos Aire		Argentina
25	11	Cordoba		Argentina
26	2	Cordoba		Argentina
27	13	Quilmes		Argentina
28	7	Rosario		Argentina
29	10	San Miguel de Tucuman		Argentina
30	6	Santa Fe		Argentina
31	18	Malvern		Australia
32	21	Maroochydore		Australia
33	23	Perth		Australia
34	179	Antwerpen		Belgium
35	199	Liege		Belgium
36	177	Merksem		Belgium
37	29	Pleven		Bulgaria
38	221	Sofia		Bulgaria
39	28	Sofia		Bulgaria
40	30	Sofia		Bulgaria
41	26	Stara Zagora		Bulgaria
42	43	Newmarket	Ontario	Canada
43	32	Toronto	Ontario	Canada
44	39	Toronto	Ontario	Canada
45	35	Hamilton		Canada
46	36	Kitchener		Canada
47	201	Pointe Claire		Canada
48	31	Sainte Foy		Canada
49	203	Winnipeg		Canada
50	190	Santiago de Chile		Chile
51	49	Santiago de Chile		Chile
52	44	Valdivia		Chile
53	52	Rijeka		Croatia
54	56	Brno		Czechia
55	57	Ostrava Trebovice		Czechia
56	187	Plzen		Czechia
57	61	Praha 2		Czechia
58	60	Praha 5		Czechia
59	55	Praha		Czechia
60	58	Uherske Hradiste		Czechia
61	62	Zlin		Czechia
62	64	Parnu		Estonia
63	65	Tallinn		Estonia
64	63	Tartu		Estonia
65	68	Hyvinkaa		Finland
66	160	Montpellier Cedex 5		France
67	71	Budapest		Hungary
68	73	Budapest		Hungary
69	75	Bupadest		Hungary
70	191	Debrecen		Hungary
71	76	Miskolc		Hungary
72	74	Szolnok		Hungary
73	79	Afula		Israel
74	82	Ashkelon		Israel
75	81	Haifa		Israel
76	83	Haifa		Israel
77	78	Ramat Gan		Israel
78	77	Tel Aviv		Israel
79	85	Zerifin		Israel
80	86	Riga		Latvia
81	88	Riga		Latvia
82	92	Alytus		Lithuania
83	89	Kaunas		Lithuania
84	91	Klaipeda		Lithuania
85	93	Panevezys		Lithuania
86	90	Siauliai		Lithuania
87	94	Vilnius		Lithuania
88	95	Mexicalli		Mexico
89	96	Monterrey		Mexico
90	103	Auckland		New Zealand
91	101	Christchurch		New Zealand
92	100	South Canterbury		New Zealand
93	192	Tauranga		New Zealand
94	107	Moscow		Russian Federation
95	113	Moscow		Russian Federation
96	222	Moscow		Russian Federation
97	223	Moscow		Russian Federation
98	224	Moscow		Russian Federation
99	109	St. Petersburg		Russian Federation
100	111	St. Petersburg		Russian Federation
101	112	St. Petersburg		Russian Federation
102	193	St. Petersburg		Russian Federation
103	110	Yaroslavl		Russian Federation
104	117	Belgrade		Serbia
105	118	Belgrade		Serbia
106	114	Niska Banja		Serbia
107	115	Novi Sad		Serbia
108	119	Bratislava		Slovakia
109	121	Kosice		Slovakia
110	120	Piestany		Slovakia
111	122	Piestany		Slovakia
112	210	Dnepropetrovsk		Ukraine
113	209	Donetsk		Ukraine
114	216	Donetsk		Ukraine
115	213	Ivano-Frankivsk		Ukraine
116	211	Kiev		Ukraine
117	212	Kiev		Ukraine
118	215	Kiev		Ukraine
119	220	Kiev		Ukraine
120	208	Symferopyl		Ukraine
121	214	Zaporozhye		Ukraine

Sponsors and Collaborators

• UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA Safety Alerts and Recalls
• Product Information

Publications

• Paul S, Marotte H, Kavanaugh A, Goupille P, Kvien TK, de Longueville M, Mulleman D, Sandborn WJ, Vande Casteele N. Exposure-Response Relationship of Certolizumab Pegol and Achievement of Low Disease Activity and Remission in Patients With Rheumatoid Arthritis. Clin Transl Sci. 2020 Jul;13(4):743-751. doi: 10.1111/cts.12760. Epub 2020 Apr 1.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00175877
• Other Study ID Numbers: C87028; 2005-001350-24
• First Posted: Sep 15, 2005
• Last Update Posted: Mar 26, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by UCB Pharma: Rheumatoid Arthritis; CDP870; Certolizumab Pegol; Cimzia
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Certolizumab Pegol

Study Results

Participant Flow

Recruitment Details	Enrollment of subjects started in June 2005. 121 centers in 22 countries enrolled subjects. Participant Flow refers to the Safety Set consisting of all enrolled subjects who received at least 1 dose of study medication. Of the 857 enrolled subjects, 846 subjects are included in the Safety Set. There was 1 enrolled subject who was never dosed.
Pre-assignment Detail	The study consists of 2 populations: of subjects who failed to achieve predefined criteria in preceding study NCT00152386 who entered C87028 on Week 16 of preceding study and of those who completed Week 52 of preceding study. Due to findings of fraud at one site, data of the 10 subjects of the site were not analyzed with data from other sites.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Period Title: Overall Study
STARTED	846
COMPLETED	497
NOT COMPLETED	349

Baseline Characteristics

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Overall Participants	846
Age (Count of Participants)
<=18 years	1 0.1%
Between 18 and 65 years	736 87%
>=65 years	109 12.9%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	51.5 (11.4)
Sex: Female, Male (Count of Participants)
Female	701 82.9%
Male	145 17.1%
Region of Enrollment (participants) [Number]
Serbia	45 5.3%
United States	56 6.6%
Estonia	16 1.9%
Slovakia	45 5.3%
Finland	5 0.6%
Ukraine	81 9.6%
Lithuania	42 5%
Russian Federation	102 12.1%
Israel	24 2.8%
Chile	11 1.3%
France	2 0.2%
Czech Republic	122 14.4%
Hungary	57 6.7%
Mexico	5 0.6%
Canada	19 2.2%
Argentina	122 14.4%
Belgium	5 0.6%
Croatia	3 0.4%
Australia	12 1.4%
Bulgaria	28 3.3%
Latvia	26 3.1%
New Zealand	18 2.1%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	73.69 (16.17)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	164.30 (8.88)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With at Least One Adverse Event (AE) From First Certolizumab Pegol (CZP) Dose up to Approximately 7 Years
Description	An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. First dose of Certolizumab Pegol (CZP) was at Baseline of the preceding double-blind study [NCT00152386] for subjects randomized to CZP, or at Entry Visit (Week 0) of this study for subjects randomized to Placebo.
Time Frame	From first dose of CZP to the end of the open-label study (approximately 7 years)

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	846
Number [percentage of participants]	94.9 11.2%

2. Primary Outcome

Title	Percentage of Subjects With at Least One Serious Adverse Event (SAE) From First Certolizumab Pegol (CZP) Dose up to Approximately 7 Years
Description	A SAE is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalisation or prolongation of existing hospitalisation Results in persistent or significant disability/incapacity, or Is a congenital anomaly or birth defect Is as infection that requires treatment parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above First dose of CZP was at Baseline of the preceding double-blind study [NCT00152386] for subjects randomized to CZP, or at Entry Visit (Week 0) of this study for subjects randomized to Placebo.
Time Frame	From first dose of CZP to the end of the open-label study (approximately 7 years)

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	846
Number [percentage of participants]	41.6 4.9%

3. Primary Outcome

Title	Percentage of Subjects Who Withdrew Due to an Adverse Event (AE) During the Study
Description	An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. The results of this Primary Outcome Measure are summarized from the Adverse Event pages of the Case Report Forms.
Time Frame	From Entry Visit (Week 0) to the end of the study (approximately 6.5 years)

Outcome Measure Data

Analysis Population Description

Safety Set

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	846
Number [percentage of participants]	16.2 1.9%

4. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 48
Description	The assessments are based on a 20 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 48 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 733 are included in this analysis. Data not available for 113 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	733
Number (95% Confidence Interval) [percentage of participants]	87.0 10.3%

5. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 96
Description	The assessments are based on a 20 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 96 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 668 are included in this analysis. Data not available for 178 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	668
Number (95% Confidence Interval) [percentage of participants]	88.0 10.4%

6. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 144
Description	The assessments are based on a 20 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 144 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 602 are included in this analysis. Data not available for 244 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	602
Number (95% Confidence Interval) [percentage of participants]	87.9 10.4%

7. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 192
Description	The assessments are based on a 20 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 192 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 537 are included in this analysis. Data not available for 309 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	537
Number (95% Confidence Interval) [percentage of participants]	89.4 10.6%

8. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Week 240
Description	The assessments are based on a 20 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 240 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 183 are included in this analysis. Data not available for 663 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	183
Number (95% Confidence Interval) [percentage of participants]	82.5 9.8%

9. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20 % Response Criteria (ACR20) at Completion/Withdrawal
Description	The assessments are based on a 20 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 20 % or more improvement in the number of swollen joints, and a 20 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 841 are included in this analysis. Data not available for 5 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	841
Number (95% Confidence Interval) [percentage of participants]	81.3 9.6%

10. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 48
Description	The assessments are based on a 50 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 48 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 733 are included in this analysis. Data not available for 113 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	733
Number (95% Confidence Interval) [percentage of participants]	63.0 7.4%

11. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 96
Description	The assessments are based on a 50 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 96 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 668 are included in this analysis. Data not available for 178 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	668
Number (95% Confidence Interval) [percentage of participants]	66.0 7.8%

12. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 144
Description	The assessments are based on a 50 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 144 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 602 are included in this analysis. Data not available for 244 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	602
Number (95% Confidence Interval) [percentage of participants]	65.4 7.7%

13. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 192
Description	The assessments are based on a 50 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 192 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 537 are included in this analysis. Data not available for 309 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	537
Number (95% Confidence Interval) [percentage of participants]	64.8 7.7%

14. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Week 240
Description	The assessments are based on a 50 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 240 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 183 are included in this analysis. Data not available for 663 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	183
Number (95% Confidence Interval) [percentage of participants]	58.5 6.9%

15. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 50 % Response Criteria (ACR50) at Completion/Withdrawal
Description	The assessments are based on a 50 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 50 % or more improvement in the number of swollen joints, and a 50 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 841 are included in this analysis. Data not available for 5 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	841
Number (95% Confidence Interval) [percentage of participants]	57.6 6.8%

16. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 48
Description	The assessments are based on a 70 % or greater improvement from Baseline to Week 48 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 48 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 733 are included in this analysis. Data not available for 113 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	733
Number (95% Confidence Interval) [percentage of participants]	37.7 4.5%

17. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 96
Description	The assessments are based on a 70 % or greater improvement from Baseline to Week 96 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 96 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 668 are included in this analysis. Data not available for 178 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	668
Number (95% Confidence Interval) [percentage of participants]	40.7 4.8%

18. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 144
Description	The assessments are based on a 70 % or greater improvement from Baseline to Week 144 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 144 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 602 are included in this analysis. Data not available for 244 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	602
Number (95% Confidence Interval) [percentage of participants]	41.2 4.9%

19. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 192
Description	The assessments are based on a 70 % or greater improvement from Baseline to Week 192 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 192 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 537 are included in this analysis. Data not available for 309 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	537
Number (95% Confidence Interval) [percentage of participants]	42.8 5.1%

20. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Week 240
Description	The assessments are based on a 70 % or greater improvement from Baseline to Week 240 in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Week 240 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 183 are included in this analysis. Data not available for 663 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	183
Number (95% Confidence Interval) [percentage of participants]	34.4 4.1%

21. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 70 % Response Criteria (ACR70) at Completion/Withdrawal
Description	The assessments are based on a 70 % or greater improvement from Baseline to Completion/Withdrawal in the number of tender joints, a 70 % or more improvement in the number of swollen joints, and a 70 % or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the preceding double-blind study.
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 841 are included in this analysis. Data not available for 5 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	841
Number (95% Confidence Interval) [percentage of participants]	38.2 4.5%

22. Secondary Outcome

Title	Change From Baseline of the Preceding Double-Blind Study to Week 96 in Modified Total Sharp Score (mTSS)
Description	The mTSS quantifies the extent of bone erosions and joint space narrowing for 44 and 42 joints, respectively, as assessed by x-rays of the hands and feet. The score ranges from 0 to 448 with higher scores representing greater damage. A negative value in mTSS change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time Frame	From Baseline of the preceding double-blind study to Week 96 of the open-label study

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 661 are included in this analysis. Data not available for 185 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	661
Mean (Standard Deviation) [units on a scale]	0.95 (4.79)

23. Secondary Outcome

Title	Change From Baseline of the Preceding Double-Blind Study to Completion/Withdrawal Visit in Health Assessment Questionnaire - Disability Index (HAQ-DI) Total Score
Description	The HAQ-DI assesses the degree of difficulty experienced in eight domains (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Gripping, Other Activities) of daily living activities using 20 questions. The HAQ-DI is calculated by summing the domain scores and dividing them by the number of domains. It ranges from 0 (no difficulty) to 3 (unable to do). Negative values indicate an improvement from Baseline to the Post-Baseline Visit with larger negative values showing a better improvement.
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 824 are included in this analysis. Data not available for 22 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	824
Mean (Standard Deviation) [units on a scale]	-0.674 (0.640)

24. Secondary Outcome

Title	Change From Baseline to Completion/Withdrawal Visit in Duration of Morning Stiffness
Description	Morning stiffness is defined as the time in hours elapsed between the time of usual awakening (even if not in the morning) and the time the subject is as limber as he/she will be during a day involving typical activities. A negative value in duration of morning stiffness change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 838 are included in this analysis. Data not available for 8 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	838
Mean (Standard Deviation) [hours]	-2.147 (3.846)

25. Secondary Outcome

Title	Change From Baseline to Completion/Withdrawal Visit in Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28[ESR])
Description	DAS28[ESR] is calculated using the Tender Joint Count (TJC), Swollen Joint Count (SJC) Erythrocyte Sedimentation Rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x lognat (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative value in DAS28[ESR] change from Baseline indicates an improvement from Baseline.
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 834 are included in this analysis. Data not available for 12 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	834
Mean (Standard Deviation) [units on a scale]	-3.222 (1.511)

26. Secondary Outcome

Title	Percentage of Subjects With Good European League Against Rheumatism (EULAR) Response at Completion/Withdrawal Visit
Description	Good EULAR response is defined as Disease Activity Score 28 [Erythrocyte Sedimentation Rate] (DAS28[ESR]) improvement from Baseline of the preceding double-blind study > 1.2 and DAS28[ESR] value < 3.2.
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 834 are included in this analysis. Data not available for 12 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	834
Number [percentage of participants]	42.4 5%

27. Secondary Outcome

Title	Change From Baseline to Completion/Withdrawal Visit in Short-Form Health Survey (SF-36) Item Questionnaire Physical Component Summary (PCS) Score
Description	The SF-36 is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept PCS score are scored to yield values between 0 (worst) and 100 (best).
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 777 are included in this analysis. Data not available for 69 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	777
Mean (Standard Deviation) [units on a scale]	8.813 (9.092)

28. Secondary Outcome

Title	Change From Baseline to Completion/Withdrawal Visit in Short-Form Health Survey (SF-36) Item Questionnaire Mental Component Summary (MCS) Score
Description	The SF-36 is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept MCS score are scored to yield values between 0 (worst) and 100 (best).
Time Frame	From Baseline of the preceding double-blind study to Completion/Withdrawal of the open-label study (up to approximately 7 years)

Outcome Measure Data

Analysis Population Description

Of the 846 subjects in the Safety Set (SS), 777 are included in this analysis. Data not available for 69 subjects.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
Measure Participants	777
Mean (Standard Deviation) [units on a scale]	4.612 (12.592)

Adverse Events

Time Frame	Adverse Events (AEs) were collected up to approximately 7 years, from first dose of Certolizumab Pegol (CZP) to the end of the open-label study.
Adverse Event Reporting Description	AEs refer to the Safety Set. Safety Set includes all enrolled subjects who received at least 1 dose of study medication.
Arm/Group Title	Certolizumab Pegol
Arm/Group Description	All patients received Certolizumab Pegol (CZP) 400 mg subcutaneously (sc) every two weeks, given as two 1 ml injections of CZP for at least six months and then 200 mg of CZP sc every two weeks, given as one 1 ml injection. Certolizumab Pegol : Strength and Form: Lyophilized product reconstituted to 1 ml containing 200 mg of Certolizumab Pegol (CZP) given as a subcutaneous injection. Dosage and Frequency: 400 mg every two weeks for at least 6 months, then 200 mg every two weeks. Duration: Until end of study.
All Cause Mortality
	Certolizumab Pegol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Certolizumab Pegol
	Affected / at Risk (%)	# Events
Total	352/846 (41.6%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/846 (0.1%)	1
Anaemia	2/846 (0.2%)	2
Neutrophilia	1/846 (0.1%)	1
Lymphadenitis	1/846 (0.1%)	1
Lymphadenopathy	1/846 (0.1%)	1
Lymphadenopathy mediastinal	1/846 (0.1%)	2
Pancytopenia	1/846 (0.1%)	1
Cardiac disorders
Aortic valve disease	1/846 (0.1%)	1
Atrioventricular block complete	1/846 (0.1%)	1
Ischaemic cardiomyopathy	1/846 (0.1%)	1
Coronary artery disease	1/846 (0.1%)	1
Cardiac failure	4/846 (0.5%)	4
Acute myocardial infarction	1/846 (0.1%)	1
Angina pectoris	4/846 (0.5%)	4
Angina unstable	2/846 (0.2%)	2
Myocardial infarction	5/846 (0.6%)	7
Myocardial ischaemia	3/846 (0.4%)	3
Mitral valve incompetence	1/846 (0.1%)	1
Myocarditis	1/846 (0.1%)	1
Arrhythmia	1/846 (0.1%)	1
Atrioventricular extrasystoles	1/846 (0.1%)	1
Extrasystoles	1/846 (0.1%)	1
Arrhythmia supraventricular	1/846 (0.1%)	1
Atrial fibrillation	6/846 (0.7%)	7
Supraventricular tachycardia	1/846 (0.1%)	1
Cardiac arrest	1/846 (0.1%)	1
Congenital, familial and genetic disorders
Arnold-Chiari malformation	1/846 (0.1%)	1
Ear and labyrinth disorders
Vertigo	1/846 (0.1%)	1
Vertigo positional	1/846 (0.1%)	1
Eye disorders
Cataract	4/846 (0.5%)	5
Macular hole	1/846 (0.1%)	2
Retinal detachment	1/846 (0.1%)	1
Gastrointestinal disorders
Abdominal hernia	1/846 (0.1%)	1
Pancreatitis	1/846 (0.1%)	1
Pancreatitis chronic	1/846 (0.1%)	1
Tooth impacted	1/846 (0.1%)	1
Hiatus hernia	1/846 (0.1%)	1
Duodenal ulcer	1/846 (0.1%)	1
Femoral hernia	1/846 (0.1%)	1
Gastric ulcer	1/846 (0.1%)	1
Gastritis	1/846 (0.1%)	1
Abdominal pain	4/846 (0.5%)	4
Gastrointestinal motility disorder	1/846 (0.1%)	1
Ileus	1/846 (0.1%)	2
Inguinal hernia	4/846 (0.5%)	4
Nausea	1/846 (0.1%)	1
Vomiting	4/846 (0.5%)	4
Megacolon	1/846 (0.1%)	1
Gastrointestinal haemorrhage	1/846 (0.1%)	1
Melaena	1/846 (0.1%)	1
Lip ulceration	1/846 (0.1%)	1
General disorders
Asthenia	1/846 (0.1%)	1
Sudden death	2/846 (0.2%)	2
Pyrexia	5/846 (0.6%)	5
Chest pain	2/846 (0.2%)	2
Non-cardiac chest pain	1/846 (0.1%)	1
Hepatobiliary disorders
Cholecystitis	3/846 (0.4%)	3
Cholecystitis acute	1/846 (0.1%)	1
Cholelithiasis	10/846 (1.2%)	10
Hepatic cyst	1/846 (0.1%)	1
Hepatitis alcoholic	1/846 (0.1%)	1
Immune system disorders
Sarcoidosis	3/846 (0.4%)	3
Allergy to arthropod bite	1/846 (0.1%)	1
Infections and infestations
Anorectal infection	1/846 (0.1%)	1
Appendicitis	3/846 (0.4%)	3
Diverticulitis	1/846 (0.1%)	1
Gastroenteritis	3/846 (0.4%)	3
Peritoneal infection	1/846 (0.1%)	1
Arthritis bacterial	6/846 (0.7%)	6
Asymptomatic bacteriuria	2/846 (0.2%)	2
Cellulitis	11/846 (1.3%)	12
Folliculitis	1/846 (0.1%)	1
Arthritis infective	2/846 (0.2%)	2
Bursitis infective	3/846 (0.4%)	3
Sialoadenitis	1/846 (0.1%)	1
Tooth abscess	1/846 (0.1%)	1
Ear infection	2/846 (0.2%)	2
Otitis media acute	1/846 (0.1%)	1
Infectious mononucleosis	1/846 (0.1%)	1
Escherichia infection	1/846 (0.1%)	1
Dacryocystitis infective	1/846 (0.1%)	1
Salpingitis	1/846 (0.1%)	1
Geotrichum infection	1/846 (0.1%)	1
Cholecystitis infective	1/846 (0.1%)	1
Herpes zoster	5/846 (0.6%)	5
Herpes zoster disseminated	1/846 (0.1%)	1
Histoplasmosis	1/846 (0.1%)	1
Abscess soft tissue	1/846 (0.1%)	1
Device related infection	3/846 (0.4%)	3
Groin abscess	1/846 (0.1%)	1
Localised infection	1/846 (0.1%)	1
Postoperative wound infection	3/846 (0.4%)	3
Wound infection	1/846 (0.1%)	1
Bronchitis	4/846 (0.5%)	4
Bronchitis acute	5/846 (0.6%)	6
Bronchitis chronic	1/846 (0.1%)	2
Bronchopneumonia	2/846 (0.2%)	2
Lobar pneumonia	2/846 (0.2%)	2
Lower respiratory tract infection	1/846 (0.1%)	1
Obstructive chronic bronchitis with acute exacerbation	1/846 (0.1%)	1
Pneumonia	29/846 (3.4%)	31
Pyothorax	2/846 (0.2%)	2
Nocardiosis	1/846 (0.1%)	1
Condyloma acuminatum	1/846 (0.1%)	1
Gastroenteritis salmonella	2/846 (0.2%)	2
Sepsis	4/846 (0.5%)	4
Urosepsis	2/846 (0.2%)	2
Burn infection	1/846 (0.1%)	1
Furuncle	2/846 (0.2%)	2
Pyoderma	1/846 (0.1%)	1
Soft tissue infection	1/846 (0.1%)	1
Subcutaneous abscess	5/846 (0.6%)	5
Pneumonia staphylococcal	1/846 (0.1%)	1
Staphylococcal bacteraemia	1/846 (0.1%)	1
Erysipelas	6/846 (0.7%)	6
Meningitis streptococcal	1/846 (0.1%)	1
Streptococcal bacteraemia	1/846 (0.1%)	1
Disseminated tuberculosis	4/846 (0.5%)	4
Pulmonary tuberculosis	9/846 (1.1%)	9
Tuberculosis	3/846 (0.4%)	3
Tuberculous pleurisy	2/846 (0.2%)	2
Acute sinusitis	2/846 (0.2%)	2
Acute tonsillitis	1/846 (0.1%)	1
Chronic sinusitis	1/846 (0.1%)	2
Chronic tonsillitis	1/846 (0.1%)	1
Laryngitis	1/846 (0.1%)	1
Laryngopharyngitis	1/846 (0.1%)	1
Nasal vestibulitis	1/846 (0.1%)	1
Pharyngitis	3/846 (0.4%)	3
Rhinitis	1/846 (0.1%)	1
Sinusitis	3/846 (0.4%)	3
Tonsillitis	4/846 (0.5%)	5
Pyelonephritis	1/846 (0.1%)	1
Pyelonephritis acute	4/846 (0.5%)	5
Urinary tract infection	5/846 (0.6%)	5
Viral infection	1/846 (0.1%)	1
Yersinia bacteraemia	1/846 (0.1%)	1
Injury, poisoning and procedural complications
Concussion	4/846 (0.5%)	5
Traumatic brain injury	1/846 (0.1%)	1
Haemothorax	1/846 (0.1%)	1
Dislocation of joint prosthesis	1/846 (0.1%)	1
Complication of device removal	1/846 (0.1%)	1
Joint dislocation	1/846 (0.1%)	1
Multiple fractures	1/846 (0.1%)	1
Anastomotic ulcer	1/846 (0.1%)	1
Joint injury	2/846 (0.2%)	2
Limb traumatic amputation	1/846 (0.1%)	1
Meniscus lesion	1/846 (0.1%)	1
Femoral neck fracture	3/846 (0.4%)	3
Femur fracture	2/846 (0.2%)	2
Foot fracture	1/846 (0.1%)	1
Hip fracture	3/846 (0.4%)	4
Lower limb fracture	6/846 (0.7%)	6
Tibia fracture	3/846 (0.4%)	3
Tendon rupture	1/846 (0.1%)	1
Excoriation	1/846 (0.1%)	1
Polytraumatism	1/846 (0.1%)	1
Wound secretion	1/846 (0.1%)	1
Post procedural haemorrhage	1/846 (0.1%)	1
Seroma	1/846 (0.1%)	2
Intentional overdose	1/846 (0.1%)	1
Overdose	2/846 (0.2%)	2
Acetabulum fracture	1/846 (0.1%)	1
Pelvic fracture	2/846 (0.2%)	2
Drug toxicity	1/846 (0.1%)	1
Neck injury	1/846 (0.1%)	1
Vertebral injury	1/846 (0.1%)	1
Contusion	2/846 (0.2%)	2
Skin laceration	2/846 (0.2%)	2
Skull fracture	1/846 (0.1%)	1
Dislocation of vertebra	2/846 (0.2%)	2
Thoracic vertebral fracture	1/846 (0.1%)	1
Rib fracture	1/846 (0.1%)	1
Forearm fracture	3/846 (0.4%)	3
Hand fracture	1/846 (0.1%)	1
Humerus fracture	2/846 (0.2%)	2
Radius fracture	1/846 (0.1%)	1
Upper limb fracture	5/846 (0.6%)	5
Wrist fracture	2/846 (0.2%)	2
Investigations
Blood creatinine increased	1/846 (0.1%)	1
Blood urea increased	1/846 (0.1%)	1
Smear cervix abnormal	1/846 (0.1%)	1
Chest X-ray abnormal	1/846 (0.1%)	2
Blood creatine phosphokinase increased	1/846 (0.1%)	1
Neutrophil count decreased	1/846 (0.1%)	1
Metabolism and nutrition disorders
Diabetes mellitus	2/846 (0.2%)	2
Hypercholesterolaemia	1/846 (0.1%)	1
Hypoglycaemia	2/846 (0.2%)	2
Ketoacidosis	1/846 (0.1%)	1
Musculoskeletal and connective tissue disorders
Arthritis	4/846 (0.5%)	5
Osteonecrosis	7/846 (0.8%)	8
Finger deformity	1/846 (0.1%)	1
Foot deformity	1/846 (0.1%)	1
Knee deformity	1/846 (0.1%)	1
Lower limb deformity	1/846 (0.1%)	3
Toe deformity	3/846 (0.4%)	3
Upper limb deformity	1/846 (0.1%)	1
Wrist deformity	1/846 (0.1%)	2
Intervertebral disc protusion	2/846 (0.2%)	2
Joint destruction	2/846 (0.2%)	2
Arthralgia	4/846 (0.5%)	4
Back pain	3/846 (0.4%)	3
Flank pain	1/846 (0.1%)	1
Pain in extremity	1/846 (0.1%)	1
Osteoarthritis	8/846 (0.9%)	9
Osteoporotic fracture	1/846 (0.1%)	1
Rheumatoid arthritis	34/846 (4%)	38
Rheumatoid nodule	1/846 (0.1%)	1
Scoliosis	1/846 (0.1%)	1
Spondylitis	1/846 (0.1%)	1
Synovial cyst	1/846 (0.1%)	1
Synovitis	1/846 (0.1%)	1
Shoulder deformity	1/846 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	3/846 (0.4%)	3
Colon cancer	2/846 (0.2%)	2
Thyroid neoplasm	1/846 (0.1%)	1
Endometrial cancer	1/846 (0.1%)	1
Gastric cancer stage IV	1/846 (0.1%)	1
Malignant peritoneal neoplasm	1/846 (0.1%)	1
Lip and/ or oral cavity cancer	1/846 (0.1%)	1
Castleman's disease	1/846 (0.1%)	1
Metastases to central nervous system	1/846 (0.1%)	1
Metastases to liver	1/846 (0.1%)	1
Metastases to lung	1/846 (0.1%)	1
Myeloproliferative disorder	1/846 (0.1%)	1
Neoplasm malignant	2/846 (0.2%)	2
Squamous cell carcinoma	1/846 (0.1%)	1
Meningioma	1/846 (0.1%)	1
Ovarian adenoma	1/846 (0.1%)	1
Ovarian germ cell teratoma benign	1/846 (0.1%)	1
Renal cell carcinoma stage II	1/846 (0.1%)	1
Small cell lung cancer stage unspecified	1/846 (0.1%)	1
Malignant melanoma	2/846 (0.2%)	2
Basal cell carcinoma	3/846 (0.4%)	4
Squamous cell carcinoma of skin	1/846 (0.1%)	1
Benign urinary tract neoplasm	1/846 (0.1%)	1
Uterine leiomyoma	3/846 (0.4%)	3
Uterine cancer	1/846 (0.1%)	1
Vaginal cancer stage 0	1/846 (0.1%)	1
Nervous system disorders
Cerebral haemorrhage	1/846 (0.1%)	1
Cerebrovascular accident	4/846 (0.5%)	5
Ischaemic cerebral infarction	1/846 (0.1%)	1
Cerebrovascular disorder	1/846 (0.1%)	1
Vertebrobasilar insufficiency	1/846 (0.1%)	1
Cervicobrachial syndrome	1/846 (0.1%)	1
Diabetic neuropathy	1/846 (0.1%)	1
Syncope	3/846 (0.4%)	3
Syncope vasovagal	1/846 (0.1%)	1
Grand mal convulsion	1/846 (0.1%)	1
Headache	2/846 (0.2%)	2
Dizziness	1/846 (0.1%)	1
Hemiparesis	1/846 (0.1%)	1
Radiculopathy	1/846 (0.1%)	1
Transient ischaemic attack	2/846 (0.2%)	2
Pregnancy, puerperium and perinatal conditions
Pregnancy	3/846 (0.4%)	3
Pregnancy on oral contraceptive	1/846 (0.1%)	1
Psychiatric disorders
Bipolar disorder	1/846 (0.1%)	1
Confusional state	1/846 (0.1%)	1
Depression	3/846 (0.4%)	4
Conversion disorder	1/846 (0.1%)	1
Suicide attempt	1/846 (0.1%)	1
Renal and urinary disorders
Stress incontinence	1/846 (0.1%)	1
Bladder prolapse	1/846 (0.1%)	1
Glomerulonephritis membranoproliferative	1/846 (0.1%)	1
Renal failure	1/846 (0.1%)	1
Renal cyst	1/846 (0.1%)	1
Haematuria	1/846 (0.1%)	1
Calculus ureteric	1/846 (0.1%)	1
Renal colic	4/846 (0.5%)	4
Reproductive system and breast disorders
Cervical dysplasia	1/846 (0.1%)	1
Cervical polyp	2/846 (0.2%)	2
Metrorrhagia	4/846 (0.5%)	4
Ovarian cyst	2/846 (0.2%)	2
Ovarian haemorrhage	1/846 (0.1%)	1
Uterine prolapse	2/846 (0.2%)	2
Vaginal prolapse	1/846 (0.1%)	1
Benign prostatic hyperplasia	1/846 (0.1%)	1
Pelvic pain	1/846 (0.1%)	1
Endometrial hyperplasia	2/846 (0.2%)	2
Uterine haemorrhage	1/846 (0.1%)	1
Uterine polyp	2/846 (0.2%)	2
Bartholin's cyst	1/846 (0.1%)	1
Vaginal haemorrhage	1/846 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/846 (0.1%)	1
Chronic obstructive pulmonary disease	4/846 (0.5%)	5
Alveolitis fibrosing	1/846 (0.1%)	1
Nasal polyps	1/846 (0.1%)	1
Emphysema	1/846 (0.1%)	1
Interstitial lung disease	1/846 (0.1%)	1
Lung infiltration	2/846 (0.2%)	2
Pleurisy	2/846 (0.2%)	2
Hydrothorax	1/846 (0.1%)	1
Pleural effusion	5/846 (0.6%)	6
Pneumothorax	1/846 (0.1%)	1
Acute pulmonary oedema	1/846 (0.1%)	1
Pulmonary embolism	5/846 (0.6%)	5
Respiratory failure	2/846 (0.2%)	2
Skin and subcutaneous tissue disorders
Dermatitis allergic	1/846 (0.1%)	1
Pityriasis rosea	1/846 (0.1%)	1
Pruritus generalised	1/846 (0.1%)	1
Purpura	1/846 (0.1%)	1
Rash	1/846 (0.1%)	1
Skin ulcer	1/846 (0.1%)	1
Urticaria	1/846 (0.1%)	1
Surgical and medical procedures
Joint arthroplasty	3/846 (0.4%)	3
Knee arthroplasty	3/846 (0.4%)	3
Synovectomy	1/846 (0.1%)	1
Brain operation	1/846 (0.1%)	1
Therapy regimen changed	1/846 (0.1%)	1
Hysterectomy	1/846 (0.1%)	1
Vascular disorders
Haematoma	1/846 (0.1%)	1
Post thrombotic syndrome	1/846 (0.1%)	1
Thrombosis	1/846 (0.1%)	1
Venous thrombosis	3/846 (0.4%)	3
Arteriosclerosis	1/846 (0.1%)	1
Deep vein thrombosis	6/846 (0.7%)	6
Trombophlebitis	1/846 (0.1%)	1
Venous thrombosis limb	3/846 (0.4%)	4
Essential hypertension	1/846 (0.1%)	1
Hypertension	2/846 (0.2%)	2
Orthostatic hypotension	1/846 (0.1%)	1
Rheumatoid vasculitis	2/846 (0.2%)	2
Vasculitis	1/846 (0.1%)	1
Vena cava thrombosis	1/846 (0.1%)	1
Other (Not Including Serious) Adverse Events
	Certolizumab Pegol
	Affected / at Risk (%)	# Events
Total	682/846 (80.6%)
Blood and lymphatic system disorders
Anaemia	57/846 (6.7%)	77
Eye disorders
Conjunctivitis	55/846 (6.5%)	77
Gastrointestinal disorders
Diarrhoea	66/846 (7.8%)	90
Nausea	53/846 (6.3%)	84
Dyspepsia	57/846 (6.7%)	76
Gastritis	48/846 (5.7%)	59
General disorders
Pyrexia	59/846 (7%)	86
Infections and infestations
Urinary tract infection	150/846 (17.7%)	280
Nasopharyngitis	158/846 (18.7%)	270
Upper respiratory tract infection	138/846 (16.3%)	267
Bronchitis acute	99/846 (11.7%)	134
Pharyngitis	86/846 (10.2%)	132
Herpes simplex	71/846 (8.4%)	131
Influenza	87/846 (10.3%)	115
Sinusitis	72/846 (8.5%)	110
Bronchitis	66/846 (7.8%)	89
Rhinitis	56/846 (6.6%)	75
Respiratory tract infection	45/846 (5.3%)	74
Investigations
Hepatic enzyme increased	45/846 (5.3%)	73
Alanine aminotransferase increased	52/846 (6.1%)	72
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	133/846 (15.7%)	225
Back pain	103/846 (12.2%)	150
Arthralgia	71/846 (8.4%)	119
Nervous system disorders
Headache	92/846 (10.9%)	140
Psychiatric disorders
Depression	43/846 (5.1%)	54
Respiratory, thoracic and mediastinal disorders
Cough	58/846 (6.9%)	77
Skin and subcutaneous tissue disorders
Rash	63/846 (7.4%)	84
Vascular disorders
Hypertension	159/846 (18.8%)	242

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.